Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | C22H38O5 |
| Molecular Weight | 382.5341 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 4 / 4 |
| E/Z Centers | 1 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
CCCCCCCC(=O)CC[C@H]1[C@H](O)C[C@H](O)[C@@H]1C\C=C/CCCC(O)=O
InChI
InChIKey=TVHAZVBUYQMHBC-SNHXEXRGSA-N
InChI=1S/C22H38O5/c1-2-3-4-5-8-11-17(23)14-15-19-18(20(24)16-21(19)25)12-9-6-7-10-13-22(26)27/h6,9,18-21,24-25H,2-5,7-8,10-16H2,1H3,(H,26,27)/b9-6-/t18-,19-,20+,21-/m1/s1
DescriptionCurator's Comment: Description was created based on several sources, including
http://www.drugs.com/ppa/unoprostone.html
http://www.drugbank.ca/drugs/DB06826
http://www.rxlist.com/rescula-drug.htm
Curator's Comment: Description was created based on several sources, including
http://www.drugs.com/ppa/unoprostone.html
http://www.drugbank.ca/drugs/DB06826
http://www.rxlist.com/rescula-drug.htm
Unoprostone Isopropyl is a synthetic docosanoid and a structural analogue of an inactive biosynthetic cyclic derivative of arachidonic acid, 13,14-dihydro-15-keto-prostaglandin F 2a. Although the mechanism of action is unknown, unoprostone isopropyl is believed to reduce elevated intraocular pressure by increasing the outflow of aqueous humor through the trabecular meshwork. Unoprostone isopropyl (UI) may have a local effect on Big Potassium channels and ClC-2 chloride channels, but the exact mechanism is unknown at this time. Unoprostone is used for the management of open-angle glaucoma and ocular hypertension. The therapeutic efficacy of Unoprostone can be decreased when used in combination with Celecoxib, Diclofenac, Diflunisal, Etodolac and some other drugs. Unoprostone isopropyl ophthalmic solution may gradually increase the pigmentation of the iris, cause pigment changes (darkening) to periorbital pigmented tissues and eyelashes, exacerbate active intraocular inflammation (e.g., uveitis), and cause macular edema. In clinical studies, the most common ocular adverse reactions with use of Rescula were burning/stinging, burning/stinging upon drug instillation, dry eyes, itching, increased length of eyelashes, and injection. These were reported in approximately 10–25% of patients. Ocular adverse reactions occurring in approximately 5–10% of patients were abnormal vision, eyelid disorder, foreign body sensation, and lacrimation disorder. Other adverse reactions occurred more rarely.
Originator
Sources: http://uk.reuters.com/article/idUS221685+22-Mar-2011+BW20110322 | http://adisinsight.springer.com/drugs/800003136
Curator's Comment: R-Tech Ueno received the first marketing approval of unoprostone isopropyl in Japan in 1994 for the treatment of Glaucoma and Ocular Hypertension.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL1987 |
3280.0 nM [EC50] |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Primary | RESCULA Approved UseRescula (unoprostone isopropyl ophthalmic solution) 0.15% is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date2000 |
|||
| Primary | RESCULA Approved UseRescula (unoprostone isopropyl ophthalmic solution) 0.15% is indicated for the lowering of intraocular pressure in patients with open-angle glaucoma or ocular hypertension. Launch Date2000 |
Cmax
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
1.5 ng/mL |
1 drop 2 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered: |
UNOPROSTONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
T1/2
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
14 min |
1 drop 2 times / day multiple, ocular dose: 1 drop route of administration: Ocular experiment type: MULTIPLE co-administered: |
UNOPROSTONE plasma | Homo sapiens population: HEALTHY age: ADULT sex: UNKNOWN food status: UNKNOWN |
Doses
| Dose | Population | Adverse events |
|---|---|---|
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Disc. AE: Abnormal vision, Burning sensation... AEs leading to discontinuation/dose reduction: Abnormal vision (1.1%) Sources: Burning sensation (0.6%) Instillation site burning (0.3%) Conjunctivitis (0.5%) Sensation of foreign body (0.6%) Asthma (0.2%) Chest pain (0.2%) Insomnia (0.3%) Rash (0.5%) |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Disc. AE: Intraocular pressure increased... AEs leading to discontinuation/dose reduction: Intraocular pressure increased (2 patients) Sources: |
AEs
| AE | Significance | Dose | Population |
|---|---|---|---|
| Asthma | 0.2% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Chest pain | 0.2% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Insomnia | 0.3% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Instillation site burning | 0.3% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Conjunctivitis | 0.5% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Rash | 0.5% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Burning sensation | 0.6% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Sensation of foreign body | 0.6% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Abnormal vision | 1.1% Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
| Intraocular pressure increased | 2 patients Disc. AE |
0.15 % 2 times / day steady, ophthalmic Recommended Dose: 0.15 %, 2 times / day Route: ophthalmic Route: steady Dose: 0.15 %, 2 times / day Sources: |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Overview
| CYP3A4 | CYP2C9 | CYP2D6 | hERG |
|---|---|---|---|
OverviewOther
| Other Inhibitor | Other Substrate | Other Inducer |
|---|---|---|
Drug as perpetrator
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes |
Drug as victim
| Target | Modality | Activity | Metabolite | Clinical evidence |
|---|---|---|---|---|
| yes [Km 93 uM] | ||||
| yes | ||||
| yes | ||||
Page: 6.0 |
yes |
PubMed
| Title | Date | PubMed |
|---|---|---|
| Effect of topical isopropyl unoprostone on macular atrophy progression in eyes with exudative age-related macular degeneration. | 2017-03 |
|
| Long-Term Protection of Genetically Ablated Rabbit Retinal Degeneration by Sustained Transscleral Unoprostone Delivery. | 2016-12-01 |
|
| Protective effects of sustained transscleral unoprostone delivery against retinal degeneration in S334ter rhodopsin mutant rats. | 2016-11 |
|
| Unoprostone activation of BK (KCa1.1) channel splice variants. | 2015-11 |
Patents
Sample Use Guides
Unoprostone isopropyl ophthalmic solution, 1.5 mg/mL. One drop in the affected eye(s) twice daily.
Route of Administration:
Topical
In Vitro Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26120274
Curator's Comment: The porcine retinal arterioles dilated in response to Unoprostone Isopropyl in a dose-dependent (100 pM-10 uM) manner. The highest concentration (10 uM) elicited about 30% of the maximal dilation.
The porcine retinal arterioles dilated in response to Unoprostone Isopropyl in a dose-dependent (100 pM-10 uM) manner. The highest concentration (10 uM) elicited about 30% of the maximal dilation.
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| Classification Tree | Code System | Code | ||
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NDF-RT |
N0000007706
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S01EE02
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C78568
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N0000007706
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QS01EE02
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N0000175454
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N0000007706
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DB06826
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C76904
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120373-36-6
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6920
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Unoprostone
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CHEMBL1201407
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1546408
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UNOPROSTONE
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39455
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m11304
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100000076642
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5311236
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SUB11381MIG
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ACTIVE MOIETY
PRODRUG (METABOLITE ACTIVE)